The gap between basic research advances and new clinical insights and treatments remains a critical obstacle to progress in the field of alcoholism research. This translational neuroscience mission is the enduring focus of the Center for the Translational Neuroscience of Alcoholism (CTNA). The CTNA conducts groundbreaking psychopharmacology, neuroimaging, molecular neuroscience, and molecular genetic studies in the service of providing new insights to bridge the gap between basic and clinical research. This renewal application will study mechanisms through which disturbances in glutamate and dopamine neurotransmission within cortico-limbic circuitry contribute to the vulnerability to persistent heavy drinking and alcohol dependence. Building on these insights, it will explore a novel approach to the pharmacotherapy of alcohol dependence that emerges directly from mechanistic CTNA research. The CTNA will facilitate transdisciplinary research within projects and between projects within the Center and will facilitate additional external collaborations. It will also continue its highly productive Pilot Projects Core that provides for an open competitive mechanism that supports innovative research and talented investigators new to the field of alcoholism research. The CTNA will continue and expand its career development mission, building on the success of its new NIAAA Research Fellowship Program. It will also continue its program of community based educational programs for lay audiences. Further it will continue to promote translational research through sponsorship of educational programs, such as the NIAAA-supported International Conference on the Applications of Neuroimaging to Alcoholism.